Figure 2.

BACE1 (beta-site amyloid precursor protein cleaving enzyme 1) and the amyloid-β (Aβ) cycle. Despite the fact that several clinical trials investigating anti-Aβ compounds did not reach primary end points, Aβ peptides, oligomers, protofibrils, and plaques still remain attractive targets. Of note, the nature of the toxic Aβ species remains unclear. Evidence suggests that, besides fibrils, dimeric or oligomeric Aβ species, but not monomeric Aβ peptides, cause neuronal hyperactivity and downstream toxicity in the vicinity of Aβ plaques.